Glucocorticoids are our best ____ agents
For treating colds and allergies, what is the major target?
What do allergies increase and what happens from this?
Histamine. This causes vasodilation so you get bigger vessels that are leaky--this causes congestion and runny nose.
For colds, what is increased and what does this cause?
Viral inflammation increases bradykinin. Bradykinin causes runny and stuffy nose (via blood vessels).
What would blocking histamine receptors help against?
Would blocking histamine receptors do anything against colds? If not, what should be done?
No, colds are not mediated through histamine, they are mediated through bradykinin. We don't have direct bradykinin inhibitors so in order to counteract bradykinin's vasodilation, we need to stimulate a1 receptors to vasoconstrict.
True or False: bradykinin can cause cough
True. It can stimulate sensory receptors that signal the cough center in the CNS. This is why ace inhibitors can cause cough.
Antihistamines are primarily used to treat ____ ____
Decongestants (vasoconstrictoors) are primarily used to treat _____ and ____
allergic rhinitis and viral cold infections
What's the difference between 1st generation and 2nd generation anti-histamines?
They are both equally effective at blocking H1 histamine receptors but they block the receptors at different locations. Thus, they have different uses and side-effects associated with them.
For treating allergies, do we typically inhibit the release of histamines or inhibit the receptors from receiving the histamines?
We inhibit the receptors. The histamines have already been released.
Cromolyn is a mast cell stabilizer that can prevent the release of histamine but in allergy treatment the histamines have been released already so we target the receptors.
How do beta adrenergic agents (epinephrine, isoproterenol) affect mast cells?
They reduce the release of mast cell contents. This may be a small anti-inflammatory effect you get from LABA for asthma or epinephrine in anaphylactic shock.
What is the pathophysiology of histamine in...
Histamine stimulates H1 receptors on endothelial cells which increases NO.
In the cardiovascular system, this causes vasodilation of the arterioles which can lead to hypotension, nasal congestion, reflex tachycardia, increased capillary permeability which can cause edema, shock, rhinorrhea, and hives.
Histamine stimulates H2 receptors which cause cardiac stiulation and vasodilation.
In the GI tract, histamine stimulates H1 receptors which cause contraction of smooth muscle (cramping) and H2 receptors which increase gastric acid secretion.
In the lungs, histamine can cause bronchoconstriction which is a hyperactive response in asthma.
In neurons, histamine can stimulate sensory nerve endings which can cause pain and/or itching.
What is an anaphylactic reactions, what causes it, and how is it treated?
Anaphylactic reactions are caused by histamine plus other mediators released from mast cells and present with urticaria, abdominal carmps, laryngospasm, bronchospasm, decreased blood pressure, and shock.
Anaphylactic reactions are treated by epinephrine (to reduce release of mast cell contents).
Antihistamines are effective to add on to epinephrine treatment but are not sufficient alone for treatment.
Which generation of antihistamines is selective for blocking peripheral H1 receptors?
2nd generation antihistamines are selective for H1 receptors in the periphery (but not in the brain)
Which generation of antihistamines has additional blocking actions at non-H1 receptors?
1st generation antihistamine agents
True or False: Both generations of antihistamines block H1 receptors equally well
Do antihistamines block reversibly or irreversibly?
What does blocking muscarinic receptors do?
Sedation (lower level of sedation in 2nd gen. bc they are highly H1 selective and less CNS penetrative)
Prevention of nausea-vomiting
What are some side effects of blocking muscarinic receptors?
Urinary retention, blurred vision, dry mouth, constipation
(no pee, no see, no spit, no shit)
Antihistamines can block sodium channels. What does this block do?
Local anesthetic action via block of Na+ channels involved in action potential generation. Most often used topically
Antihistamines can block a1-adrenergic receptors. What does this block do?
This blocks vasoconstriction and can cause orthostatic hypotension in susceptible individuals.
For allergic reactions (rhinitis-urticaria) would you use 1st or 2nd generation antihistamines?
Either. They both do H1 receptor block
For cough suppression, what channel do you need to block and what generation antihistamine would be used?
Na+ channel block which can be done by 1st generation antihistamines.
For suppressing motion sickness, which receptor(s) do you need to block and what generation antihistamine can be given for this?
You need to block H1 and muscarinic receptors to interrupt the visceral afferent pathway to vestibular nucli. You do this by giving a 1st generation antihistamine.
2nd generation doesn't get into the brain so you can't use that... also 2nd generation are selective for H1 and don't do much to muscrinic receptors.
Do 1st or 2nd generation histamines penetrate into the CNS?
For suppressing nausea-vomiting of pregnancy, which receptors need to be blocked and which antihistamine generation can be given to do this?
H1 and muscarinic receptors by 1st generation antihistamines.
Antihistamines can be used as a sleep aid for insomnia. Which receptors need to be blocked for this effect and which generation antihistamine does this?
H1 and muscarinic receptor block. This is done with 1st generation antihistamines.
True or False: onset for antihistamines is slow
False! It's rapid
True or False: corticosteroids are very effective at treating allergic disorders quickly
False. While corticosteroids are very effective at treating allergic disorders, the onset of action is slow (on the order of days).
This is because they need to go into the nucleus to change transcription.
C. Overuse associated with rebound congestion
F. More effective than pseudoephedrine for viral cold symptoms
What are side effects of antihistamines?
Sedation (prominent with 1st generation agents like diphenhydramine and minimal with 2nd generation bc it doesn't cross the blood brain barrier)
Antimuscarinic action (dry mouth, urinary retension, constipation, blurry vision)
Paradoxical excitation (most patients will experience sedation but occasionally you see excitability. weird.)
Postural hypotension (from a1 block- more with promethazine)
GI effects (loss of appetite, nausea/vomiting - taking with food or water eliminates this effect)
B. Dry mouth
Name 3 first-generation antihistamines
Name 3 second-generation antihistamines
Of the 3 first-generation antihistamines, which gives the least drowsiness?
What are antiemetic effects?
An antiemetic is a drug that is effective against vomiting and nausea. Antiemetics are typically used to treat motion sickness and the side effects of opioid analgesics, general anaesthetics, and chemotherapy directed against cancer.
Are 1st or 2nd generation antihistamines used for antiemetic effects?
Are 1st generation or 2nd generation antihistamines longer acting?
2nd generation antihistamines
While all first-generation antihistamines have antiemetic effects, which is most commonly used for its antiemetic ability?
Meclizine. Meclizine has the least sedative effects and most antiemetic effects.
C. 2nd generation agents are not effective in the OTC treatment of insomnia
F. 1st generation agents are effective in the OTC treatment of insomnia
What receptor(s) do decongestants target?
alpha 1 receptors in vessels
What are 4 cold symptoms and how do rhinoviruses cause these symptoms?
The viruses attach to respiratory cells which generates inflammatory mediators including bradykinin. Bradykinin causes the cold symptoms:
1. Pain (via activation of nociceptors)
2. Nasal stuffiness (via dilation of blood vessels)
3. Nasal fluid hypersecretion (via increased capillary permeability plus parasympathetic reflex mechanisms)
4. Cough (via activation of irritant sensory receptors)
True or False: Mast cell mediators (histamine) have a major role in the viral inflammatory response.
False. They have a minor role in the viral inflammatory response (colds)
What's the mechanism for topical decongestants?
They stimulate alpha 1 receptors of nasal blood vessels that are dilated by histamine or bradykinin. This causes vasoconstriction which promotes drainage and improves breathing.
What are side effects of topical decongestants and why are patients prone to developing these effects?
Topical decongestants cause a prompt effect relative to oral decongestants which can lead to tendency of overuse. When you vasoconstrict too much, you decrease flood flow and oxygenation of tissue causing tissue damange and inflammation. Patients usually think that the medication used to work but stopped working so they try using more and more of it which actually makes the problem worse causing rebound congestion (rhinitis medicamentosa) due to ischemia-local irritation.
Name 2 topical decongestants and what the differences are between the two
1. Phenylephrine (neosynephrine) is the most effective agent, is shorter in duration, and may produce marked irritation in some
2. Oxymetazoline (Afrin) is longer acting (6-12 hr duration); used twice/day, and limits rebound congestion.
Does phenylephrine or oxymetazoline have a higher likelihood of causing rhinitis medicamentosa?
What's the mechanism of action for oral decongestants?
Oral decongestants stimulate alpha1 receptors of nasal blood vessels dilated by histamine or bradykinin which causes vasoconstriction. The decongestants are delivered via systemic circulation to the nasal vascular bed. Oral decongestants are less intense but have a longer duration of action compared to topical.
What are side effects for oral decongestants?
Systemic actions can cause headaches, nausea, dizziness, and increased BP-palpitations (chronic high doses)
Name 2 oral decongestants and describe the difference between the them
1. Pseudoephedrine (Sudafed) is the safest and most effective of oral agents. When pseudoephedrine passes through the liver, it is not metabolized by MAO.
2. Phenylephrine (sudafed PE) is less safe orally because when it passes through the liver it is metabolized by hepatic MAO which causes variable interpatient blood levels. The duration of this drug is about 4 hours. (remember, phenylephrine is very effective to take topically though)
A. Effective against rhinorrhea and congestion due to allergies
E. More reliable oral bioavailability than phenylephrine
H. Increases neuronal release of NE
Antihistamines are great for ____ rhinitis but not ____ rhinitis
If a patient has high BP, should you avoid giving them oral or topical decongestants?
Avoid giving oral decongestants (e.g. pseudoephedrine) to patients with high BP or cardiovascular problems because one of the side effects is increased BP and palpitations.
If a patient's HTN is controlled, a dose of pseudoephedrine here and there won't hurt them but don't give chronically.
True or False: Decongestants do very little for cough.
True. Decongestants are for runny and stuffy noses
What are antitussive agents used for?
They are used to reduce the frequency of cough, especially dry, non-productive cough. Excessive coughing can be discomforting and self-perpetuating.
What is the mechanism of action for antitussive agents? What are some antitussive agents?
Antitussive agents have both central and peripheral actions.
The most effective agents are agonists at endogenous u-opioid receptors to depress the cough center in the brain stem.
Diphenhydramine is generally less effective, as it works through antihistaminic and/or local anesthetic actions.
Codeine, hydrocodone, and hydromorphone are opioid drugs (controlled substances) and are effective antitussives at lower doses.
Dextromethorphan (Robitussin DM) is the most commonly used OTC cough suppressant. It has variable effectiveness. It is an opioid agonist but does not depress respiration or predispose to addiction (only l-isomers do this). Mild adverse effects include drowsiness and GI upset. 15-30mg suppresses cough while 500-1500mg is drug abuse ("robo tripping")
Diphenhydramine (a 1st generation antihistamine) can also be safe and somewhat effective as an antitussive. It has a greater propensity for side effects (sedation, anti-muscarinic effects) than dextromethorphan.
Benzonatate is a top 100 drug. Tetracaine (local anesthetic) congener.
What are the most common adverse effects of antitussive agents?
Nausea, drowsiness, constipation, and (less commonly) allergic reactions
True or False: When opioid drugs should only be given short term
True. You don't want to build physiological or psychological dependence
What are guidelines for treatment for acute cough due to common cold in adults?
1st generation antihistamine/decongestant (e.g. brompheniramine/pseudoephedrine)
Naproxen (TID x 5 days) blocks inflammation that stimulates cough afferents
What are guidlines for treatment of cough in adults with upper airway cough syndrome (postnasal drip)?
1st generation antihistamine/decongestant (e.g. brompheniramine/pseudoephedrine)
C. An NSAID like naproxen may be of benefit in coughs due to common cold viruses